Abstract We have long taken for granted to rely on the current HIV recombinant classification system for various aspects of HIV recombination study. However, the central line of this system is flawed in that the viral evolution - an intrinsic feature to HIV - has not been taken into account in the establishment of recombinant families. As a result, each recombinant family defined by the current naming system literally depicts a cross-sectional view of the viral evolution. And in practice, a lack of a dynamic and evolutionary view of virus trajectory would render the design of vaccine and antiviral suboptimal. To address such a flaw in the HIV recombinant classification system, here we propose a novel methodology and research pipeline that will be performed through the following specific aims: In Aim 1, we will determine an actual, up-to-date sequence list of worldwide HIV recombinant strains, which will form the basis for determining HIV recombinant families; and in Aim 2, we will develop a novel methodology to integrate viral evolution in clustering recombinant families. Importantly, our proposed methodology does not require prior knowledge of family reference strains, thus avoiding possible bias caused by an inappropriate selection of family references. Given the biological importance of HIV recombination and a growing prevalence of HIV recombinants in both global and regional epidemics, our proposed study is important in that we address a flaw in the recombinant classification system, which sets the basis for genomic-based health care and prevention targeting epidemically important recombinant strains. Our proposed study would be the first of its kind to address such a flaw in the recombinant classification system. We will benefit from our decade- long research in HIV molecular epidemiology and extensive experience with algorithm and analysis program development to perform this proposed study. By the end of this study, we expect to obtain a dynamic vision of individual HIV recombinant families, which would help improve the design of vaccine and antivirals targeting recombinant epidemics. Finally, the novel strategy developed in this study can be easily applied to other viruses that have encountered similar problems in recombinant clustering.